Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma.

BACKGROUND: Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of the greatest concerns for patients with AFP-positive HCC. This study aimed to demonstrate the utilization of six machine learning (ML)-based prognostic models to predict overall survival of patients with AFP-positive HCC. METHODS: Data on patients with AFP-positive HCC were extracted from the Surveillance, Epidemiology, and End Results database. Six ML algorithms (extreme gradient boosting [XGBoost], logistic regression [LR], support vector machine [SVM], random forest [RF], K-nearest neighbor [KNN], and decision tree [ID3]) were used to develop the prognostic models of patients with AFP-positive HCC at one year, three years, and five years. Area under the receiver operating characteristic curve (AUC), confusion matrix, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. RESULTS: A total of 2,038 patients with AFP-positive HCC were included for analysis. The 1-, 3-, and 5-year overall survival rates were 60.7%, 28.9%, and 14.3%, respectively. Seventeen features regarding demographics and clinicopathology were included in six ML algorithms to generate a prognostic model. The XGBoost model showed the best performance in predicting survival at 1-year (train set: AUC = 0.771; test set: AUC = 0.782), 3-year (train set: AUC = 0.763; test set: AUC = 0.749) and 5-year (train set: AUC = 0.807; test set: AUC = 0.740). Furthermore, for 1-, 3-, and 5-year survival prediction, the accuracy in the training and test sets was 0.709 and 0.726, 0.721 and 0.726, and 0.778 and 0.784 for the XGBoost model, respectively. Calibration curves and DCA exhibited good predictive performance as well. CONCLUSIONS: The XGBoost model exhibited good predictive performance, which may provide physicians with an effective tool for early medical intervention and improve the survival of patients.

FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.

BACKGROUND AND AIMS: NAFLD comprises a spectrum of liver disorders with the initial abnormal accumulation of lipids in hepatocytes called NAFL, progressing to the more serious NASH in a subset of individuals. Our previous study revealed that global flavin-containing monooxygenase 2 (FMO2) knockout causes higher liver weight in rats. However, the role of FMO2 in NAFLD remains unclear. Herein, we aimed to determine the function and mechanism of FMO2 in liver steatosis and steatohepatitis. APPROACH AND RESULTS: The expression of FMO2 was significantly downregulated in patients with NAFL/NASH and mouse models. Both global and hepatocyte-specific knockout of FMO2 resulted in increased lipogenesis and severe hepatic steatosis, inflammation, and fibrosis, whereas FMO2 overexpression in mice improved NAFL/NASH. RNA sequencing showed that hepatic FMO2 deficiency is associated with impaired lipogenesis in response to metabolic challenges. Mechanistically, FMO2 directly interacts with SREBP1 at amino acids 217-296 competitively with SREBP cleavage-activating protein (SCAP) and inhibits SREBP1 translocation from the endoplasmic reticulum (ER) to the Golgi apparatus and its subsequent activation, thus suppressing de novo lipogenesis (DNL) and improving NAFL/NASH. CONCLUSIONS: In hepatocytes, FMO2 is a novel molecule that protects against the progression of NAFL/NASH independent of enzyme activity. FMO2 impairs lipogenesis in high-fat diet-induced or choline-deficient, methionine-deficient, amino acid-defined high-fat diet-induced steatosis, inflammation, and fibrosis by directly binding to SREBP1 and preventing its organelle translocation and subsequent activation. FMO2 thus is a promising molecule for targeting the activation of SREBP1 and for the treatment of NAFL/NASH.

Engineering dynamical photon blockade with Liouville exceptional points.

We investigate the dynamical blockade in a nonlinear cavity and demonstrate the connection between the correlation function g(2)(t) and system parameters in the entire nonlinear region. Utilizing the Liouville exceptional points (LEPs) and quantum dynamics, a near-perfect single-photon blockade (1PB) can be achieved. By fine-tuning system parameters to approach the second-order LEP (LEP2), we improved single-photon statistics in both weak and strong nonlinearity regimes, including a significant reduction of g(2)(t) and a pronounced increase in the single-photon occupation number. In the strong nonlinearity region, the maximum photon population may correspond to stronger antibunching effect. Simultaneously, the time window and period of blockade can be controlled by selecting detuning based on the LEP2. Furthermore, the 1PB exhibits robustness against parameter fluctuations, and this feature can be generalized to systems for implementing single-photon sources with nonharmonic energy levels.

First Potassium Fluoroaluminate Ionic Exchanger for Rapid and Selective Removal of Sr2+ with High Capacity.

90Sr, as a typical artificial radionuclide, poses a serious threat to human health and the ecological environment. The selective removal of this radionuclide from industrial nuclear waste is crucial for our environment. Here we report a novel potassium fluoroaluminate, K2[(AlF5)H2O], which was synthesized by a simple low-temperature one-step method. It adopts a 1D AlF6-chain structure, which consists of exchangeable potassium ions in between the infinite chains of octahedral Al centers. As a remarkable inorganic ionic exchanger, K2[(AlF5)H2O] has a high chemical stability (resistance of pH=~3-12) and thermal stability (≥~300 °C). It possesses an excellent adsorption selectivity (Kd=~6.1×104 mL ⋅ g-1) and a maximum adsorption capacity of qm=~120.32 mg ⋅ g-1 for Sr2+. Importantly, it still keep a very good selectivity for Sr2+ ions even in the presence of competing Na+, Mg2+ and Ca2+ aqueous solutions. K2[(AlF5)H2O] is the first example of fluoroaluminate ionic exchange materials that can capture Sr2+. This result opens up a new way to design and synthesize inorganic ionic exchangers for the selective removal of Sr2+ ions from radioactive waste water.

Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis.

BACKGROUND: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown. METHODS: Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using postn-promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI. RESULTS: A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling. CONCLUSIONS: Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Evaluation of extravascular lung water and cardiac function in normal vaginal delivery by intrapartum bedside ultrasound.

BACKGROUND: Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function. METHODS: This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed. RESULTS: During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021). CONCLUSIONS: During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.

Multi-omics analysis for ferroptosis-related genes as prognostic factors in cutaneous melanoma. / é“æ­»äº¡ç›¸å ³åŸºå› ä½œä¸ºçš®è‚¤é»‘è‰²ç´ ç˜¤é¢„åŽå› ç´ çš„å¤šç»„å­¦åˆ†æžï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Melanoma is highly malignant and heterogeneous. It is essential to develop a specific prognostic model for improving the patients' survival and treatment strategies. Recent studies have shown that ferroptosis results from the overproduction of lipid peroxidation and is an iron-dependent form of programmed cell death. Despite this, ferroptosis-related genes (FRGs) and their clinical significances remain unknown in malignant melanoma. This study aims to assess the role of FRGs in melanoma, with the goal of developing a novel prognostic model that provides new insights into personalized treatment and improvement of therapeutic outcomes for melanoma. METHODS: We systematically characterized the genetic alterations and mRNA expression of 73 FRGs in The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) dataset in this study. The results were validated with real-time RT-PCR and Western blotting. Subsequently, a multi-gene feature model was constructed using the TCGA-SKCM cohort. Melanoma patients were classified into a high-risk group and a low-risk group based on the feature model. As a final step, correlations between ferroptosis-related signatures and immune features, immunotherapy efficacy, or drug response were analyzed. RESULTS: By analyzing melanoma samples from TCGA-SKCM dataset, FRGs exhibited a high frequency of genetic mutations and copy number variations (CNVs), significantly impacting gene expression. Additionally, compared with normal skin tissue, 30 genes with significantly differential expression were identified in melanoma tissues. A prognostic model related to FRGs, constructed using the LASSO Cox regression method, identified 13 FRGs associated with overall survival prognosis in patients and was validated with external datasets. Finally, functional enrichment and immune response analysis further indicated significant differences in immune cell infiltration, mutation burden, and hypoxia status between the high-risk group and the low-risk group, and the model was effective in predicting responses to immunotherapy and drug sensitivity. CONCLUSIONS: This study develops a strong ferroptosis-related prognostic signature model which could put forward new insights into target therapy and immunotherapy for patients with melanoma.

Machine learning radiomics of magnetic resonance imaging predicts recurrence-free survival after surgery and correlation of LncRNAs in patients with breast cancer: a multicenter cohort study.

BACKGROUND: Several studies have indicated that magnetic resonance imaging radiomics can predict survival in patients with breast cancer, but the potential biological underpinning remains indistinct. Herein, we aim to develop an interpretable deep-learning-based network for classifying recurrence risk and revealing the potential biological mechanisms. METHODS: In this multicenter study, 1113 nonmetastatic invasive breast cancer patients were included, and were divided into the training cohort (n = 698), the validation cohort (n = 171), and the testing cohort (n = 244). The Radiomic DeepSurv Net (RDeepNet) model was constructed using the Cox proportional hazards deep neural network DeepSurv for predicting individual recurrence risk. RNA-sequencing was performed to explore the association between radiomics and tumor microenvironment. Correlation and variance analyses were conducted to examine changes of radiomics among patients with different therapeutic responses and after neoadjuvant chemotherapy. The association and quantitative relation of radiomics and epigenetic molecular characteristics were further analyzed to reveal the mechanisms of radiomics. RESULTS: The RDeepNet model showed a significant association with recurrence-free survival (RFS) (HR 0.03, 95% CI 0.02-0.06, P < 0.001) and achieved AUCs of 0.98, 0.94, and 0.92 for 1-, 2-, and 3-year RFS, respectively. In the validation and testing cohorts, the RDeepNet model could also clarify patients into high- and low-risk groups, and demonstrated AUCs of 0.91 and 0.94 for 3-year RFS, respectively. Radiomic features displayed differential expression between the two risk groups. Furthermore, the generalizability of RDeepNet model was confirmed across different molecular subtypes and patient populations with different therapy regimens (All P < 0.001). The study also identified variations in radiomic features among patients with diverse therapeutic responses and after neoadjuvant chemotherapy. Importantly, a significant correlation between radiomics and long non-coding RNAs (lncRNAs) was discovered. A key lncRNA was found to be noninvasively quantified by a deep learning-based radiomics prediction model with AUCs of 0.79 in the training cohort and 0.77 in the testing cohort. CONCLUSIONS: This study demonstrates that machine learning radiomics of MRI can effectively predict RFS after surgery in patients with breast cancer, and highlights the feasibility of non-invasive quantification of lncRNAs using radiomics, which indicates the potential of radiomics in guiding treatment decisions.

High Curvature PEDOT:PSS Transport Layer Toward Enhanced Perovskite Light-Emitting Diodes.

The rapidly developed metal halide perovskite light-emitting diodes (PeLEDs) are considered as a promising candidate for next-generation display and illumination, but the unbalanced charge transport is still a hard-treat case to restrict its efficiency and operational stability. Here, a high curvature PEDOT:PSS transport layer is demonstrated via the self-assembly island-like structures by the incorporation of alkali metal salts. Benefiting from the dielectric confinement effect of the high curvature surface, the modified CsPbBr3 -based PeLEDs present a 2.1 times peak external quantum efficiency (EQE) from 6.75% to 14.23% and a 3.3 times half lifetime (T50 ) from 3.96 to 13.01 h. Besides, the PeLEDs show high luminance up to 44834 cd m-2 . Evidently, this work may provide a deep insight into the structure-activity relationship between the micro-structures at the PEDOT:PSS/perovskite interface and the performance of PeLEDs, and crack the codes for ameliorating the performance of PeLEDs via interfacial micro-structured regulation.

CD45- erythroid progenitor cells promote lymph node metastasis in gastric cancer by inducing a hybrid epithelial/mesenchymal state in lymphatic endothelial cells.

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.

Identification of the potential TLR7 antagonists by virtual screening and experimental validation.

Toll-like receptor 7 (TLR7) is highly expressed in dendritic cells (DCs) and B cells, and its aberrant activation can promote disease progression in systemic lupus erythematosus (SLE). We utilized structure-based virtual screening and experimental validation to screen natural products from TargetMol for potential TLR7 antagonists. Our results of molecular docking and molecular dynamics simulation showed that Mogroside V (MV) strongly interacted with TLR7, with stable open-TLR7-MV and close-TLR7-MV complexes. Furthermore, in vitro experiments demonstrated that MV significantly inhibited B cell differentiation in a concentration-dependent manner. In addition to TLR7, we also revealed a strong interaction of MV with all TLRs, including TLR4. The above results suggested that MV might be a potential TLR7 antagonist deserving of further study.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Impact of three surgical approaches on the therapeutic efficacy of intraventricular craniopharyngiomas: a single-center retrospective analysis.

This study aimed to investigate the therapeutic efficacy of three different surgical approaches for the treatment of intraventricular craniopharyngiomas (IVCs). The three surgical approaches investigated in this study were the endoscopic endonasal approach (EEA), pterional trans-lamina terminalis approach (PTA), and interhemispheric trans-lamina terminalis approach (ITA). Patient demographics, preoperative symptoms, endocrine and hypothalamic status, tumor characteristics, and surgical outcomes were analyzed and compared among the different surgical groups. A total of 31 patients with IVCs were included in the analysis, with 12 patients in the EEA group, 8 patients in the ITA group, and 11 patients in the PTA group. The mean follow-up time was 39 ± 23 months. Statistical analysis of the data revealed significant differences in the gross total resection (GTR) rate among the three surgical groups (P = 0.033). The GTR rate for the EEA group was 100%, that for the ITA group was 88%, and that for the PTA group was 64%, which was the lowest rate observed. After surgery, only 8.3% of the patients in the EEA group did not experience new postoperative hypopituitarism, while the percentages in the ITA and PTA groups were 75% and 73%, respectively (P = 0.012). Finally, we found that postoperative hypopituitarism may be related to the transection of the pituitary stalk during the operation (P = 0.020). Based on the results of this study, we recommend using the EEA and the ITA instead of the PTA for the surgical resection of IVCs. Furthermore, the appropriate surgical approach should be selected based on the tumor's growth pattern.

Use of Sound Touch Elastography and Sound Touch Quantification for the Noninvasive Evaluation of Portal Hypertension in a Rat Model.

OBJECTIVES: In this study, we used the recently developed ultrasound elastography techniques sound touch elastography (STE) and sound touch quantification (STQ) to quantify portal hypertension (PHT) severity in a rat model of carbon tetrachloride (CCl4 )-induced cirrhotic PHT. METHODS: In total, 60 rats were used. Various degrees of PHT were established. Liver and spleen stiffness were measured by STE (L-STE and S-STE, respectively) and STQ (L-STQ and S-STQ, respectively). We measured portal pressure (PP) after ultrasonographic examination. The performance of the STE and STQ parameters in the identification of PHT was evaluated using receiver operating characteristic (ROC) analyses. RESULTS: Liver and spleen stiffness measurements obtained with STE and STQ correlated positively with the PP (r = 0.566-0.882, all P < .001). The areas under ROC curves for L-STE, S-STE, L-STQ, and S-STQ values were 0.931 (95% confidence interval [CI], 0.847-1.000), 0.982 (95% CI, 0.956-1.000), 0.796 (95% CI, 0.680-0.912), and 0.925 (95% CI, 0.858-0.993), respectively, for PP ≥5 mmHg; 0.937 (95% CI, 0.865-1.000), 0.938 (95% CI, 0.864-1.000), 0.967 (95% CI, 0.923-1.000), and 0.960 (95% CI, 0.897-1.000), respectively, for PP ≥10 mmHg; and 0.954 (95% CI, 0.897-1.000), 0.790 (95% CI, 0.652-0.928), 0.808 (95% CI, 0.680-0.935), and 0.740 (95% CI, 0.595-0.885), respectively, for PP ≥12 mmHg. CONCLUSIONS: STE and STQ are reliable noninvasive tools for the assessment of PHT severity, especially for PP ≥10 mmHg, in a rat model of CCl4 -induced cirrhotic PHT.

Performance of two-dimensional shear wave elastography for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia: a systematic review and meta-analysis.

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) has been proposed for detecting liver fibrosis in biliary atresia. OBJECTIVES: To assess the performance of 2D-SWE for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia. MATERIALS AND METHODS: Five electronic databases were searched to identify studies investigating the performance of 2D-SWE for diagnosing liver fibrosis in biliary atresia in children. We constructed the summary receiver operating characteristic (SROC) curves of 2D-SWE for detecting advanced liver fibrosis and cirrhosis, and then calculated the area under the SROC curves (AUROCs). RESULTS: Six studies with 470 patients (ages 55 days to 6.6 years) were included. The median correlation coefficient of 2D-SWE with pathological liver fibrosis stages was 0.779 (range: 0.443‒0.813). The summary AUROCs for advanced liver fibrosis and cirrhosis were 0.929 and 0.883, respectively. The summary sensitivity and specificity of 2D-SWE for advanced liver fibrosis were 88% (95% confidence interval [CI]: 80‒94%) and 85% (95% CI: 77‒91%) with I values of 0% and 45.6%, respectively, and for cirrhosis were 80% (95% CI: 72‒87%) and 82% (95% CI: 77‒86%) with I values of 12.9% and 0%, respectively. The diagnostic odds ratio (DOR) of 2D-SWE for advanced liver fibrosis and cirrhosis were 40.3 (95% CI: 18.2‒89.4) and 18.9 (95% CI: 11.2‒31.7), respectively. For preoperative detection of cirrhosis, the pooled AUROC, sensitivity, specificity, and DOR based on the four 2D-SWE studies were 0.877, 79% (95% CI: 71‒86%), 82% (95% CI: 77‒86%), and 17.58 (95% CI: 10.35‒29.85), respectively. CONCLUSIONS: Results show that 2D-SWE has potential as a non-invasive tool for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia.

Ride the dust: linking dust dispersal and spatial distribution of microorganisms across an arid landscape.

In arid ecosystems, where the soil is directly exposed to the action of the wind due to sparse vegetation, dust aerosolization is a consequence of soil degradation and concomitantly, a major vector of microbial dispersal. Disturbances such as livestock grazing or fire can exacerbate wind erosion and dust production. Here, we sampled surface soils in 29 locations across an arid landscape in southwestern USA and characterized their prokaryotic and fungal communities. At four of these locations, we also sampled potential fugitive dust. By comparing the composition of soil and dust samples, we determined the role of dust dispersal in structuring the biogeography of soil microorganisms across the landscape. For Bacteria/Archaea, we found dust associated taxa to have on average, higher regional occupancies compared to soil associated taxa. Complementarily, we found dust samples to harbour a higher amount of widely distributed taxa compared to soil samples. Overall, our study shows how dust dispersal plays a role in the spatial distribution of soil Bacteria/Archaea, but not soil Fungi, and might inform indicators of soil health and stability in arid ecosystems.

A Noninvasive Tool Based on Magnetic Resonance Imaging Radiomics for the Preoperative Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.

PURPOSE: This study aimed to identify patients with pathological complete response (pCR) and make better clinical decisions by constructing a preoperative predictive model based on tumoral and peritumoral volumes of multiparametric magnetic resonance imaging (MRI) obtained before neoadjuvant chemotherapy (NAC). METHODS: This study investigated MRI before NAC in 448 patients with nonmetastatic invasive ductal breast cancer (Sun Yat-sen Memorial Hospital, Sun Yat-sen University, n = 362, training cohort; and Sun Yat-sen University Cancer Center, n = 86, validation cohort). The tumoral and peritumoral volumes of interest (VOIs) were segmented and MRI features were extracted. The radiomic features were filtered via a random forest algorithm, and a supporting vector machine was used for modeling. The receiver operator characteristic curve and area under the curve (AUC) were calculated to assess the performance of the radiomics-based classifiers. RESULTS: For each MRI sequence, a total of 863 radiomic features were extracted and the top 30 features were selected for model construction. The radiomic classifiers of tumoral VOI and peritumoral VOI were both promising for predicting pCR, with AUCs of 0.96 and 0.97 in the training cohort and 0.89 and 0.78 in the validation cohort, respectively. The tumoral + peritumoral VOI radiomic model could further improve the predictive accuracy, with AUCs of 0.98 and 0.92 in the training and validation cohorts. CONCLUSIONS: The tumoral and peritumoral multiparametric MRI radiomics model can promisingly predict pCR in breast cancer using MRI images before surgery. Our results highlighted the potential value of the tumoral and peritumoral radiomic model in cancer management.

Detection of liver and spleen stiffness in rats with portal hypertension by two-dimensional shear wave elastography.

BACKGROUND: The measurement of liver stiffness (LS) and spleen stiffness (SS) based on ultrasound elastography can be used for non-invasive assessment of portal hypertension (PH). However, there are few studies on the corresponding mechanism of increased spleen stiffness. Our aim was to use two-dimensional shear wave elastrography (2D-SWE) to evaluate the relationship between LS and SS and the severity of PH in rats. And explore the mechanism of the increase of LS and SS in PH. METHODS: Sixty male Sprague-Dawley rats were randomly divided into portal hypertension (PH group, n = 45) and normal control (NC group, n = 15). At 12 weeks, LS and SS was detected by 2D-SWE in vivo. Related hemodynamic parameters and portal vein pressure (PVP) was measured. Spleen and liver 2D-SWE detection was performed again after sacrifice. Pathological changes were observed. RESULTS: The SS and LS were increased in PH group (P < 0.05). The SS decreased after sacrifice, and what's more the magnitude of SS decline significantly higher in PH group than in NC group (P < 0.05). The correlation between SS and PVP is stronger than LS (r = 0.624, P < 0.001). SS has positive correlation with indexes of hyperdynamic circulation, but LS was weakly. The correlation between SS and the pathological grade (r = 0.633, P < 0.001) was lower than that in LS (r = 0.905, P < 0.001). Multiple linear regression analysis revealed that SS, portal vein inner diameter (PVD) and splenic vein blood flow velocity (SVV) were significantly associated with PH. CONCLUSIONS: Spleen and liver measurement by 2D-SWE may be helpful in evaluating PVP. The correlation between SS and PVP is stronger than LS in rats measured by 2D-SWE. Hemodynamic circulation are important in the elevation of SS with portal hypertension. Pathological changes also have a degree of influence, but have more significance for the elevation of LS. SS may be a more effective noninvasive predictor of PH than LS.

Two-dimensional shear wave elastography: a new tool for evaluating respiratory muscle stiffness in chronic obstructive pulmonary disease patients.

BACKGROUND: Impaired respiratory function caused by respiratory muscle dysfunction is one of the common consequences of chronic obstructive pulmonary disease (COPD). In this study, two-dimensional shear wave elastography (2D-SWE) was used to measure diaphragm stiffness (DS) and intercostal muscle stiffness (IMS) in patients with COPD; in addition, the value of 2D-SWE in evaluating respiratory function was determined. METHODS: In total, 219 consecutive patients with COPD and 20 healthy adults were included. 2D-SWE was used to measure the DS and IMS, and lung function was also measured. The correlation between respiratory muscle stiffness and lung function and the differences in respiratory muscle stiffness in COPD patients with different severities were analysed. RESULTS: 2D-SWE measurements of the DS and IMS presented with high repeatability and consistency, with ICCs of 0.756 and 0.876, respectively, and average differences between physicians of 0.10 ± 1.61 and 0.07 ± 1.65, respectively. In patients with COPD, the DS and IMS increased with disease severity (F1 = 224.50, F2 = 84.63, P < 0.001). In patients with COPD, the correlation with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), predicted FEV1% value, residual volume (RV), total lung capacity (TLC), RV/TLC, functional residual capacity (FRC) and inspiratory capacity (IC) of DS (r1=-0.81, r2=-0.63, r3 = 0.65, r4 = 0.54, r5 = 0.60, r6 = 0.72 and r7=-0.41, respectively; P < 0.001) was stronger than that of IMS (r1=-0.76, r2=-0.57, r3 = 0.57, r4 = 0.47, r5 = 0.48, r6 = 0.60 and r7=-0.33, respectively; P < 0.001). CONCLUSION: 2D-SWE has potential for use in evaluating DS and IMS. A specific correlation was observed between respiratory muscle stiffness and lung function. With the worsening of the severity of COPD and the progression of lung function impairment, the DS and IMS gradually increased.

Isolation, Characterization of Bamboo Leaf Flavonoids by Size Exclusion Chromatography and Their Antioxidant Properties.

The utilization of bamboo industry exhibits varied but still needs to be improved. Bamboo leaf flavonoid (BLF) is an important resource of bamboo which has become a research focus. However, the isolation and purification techniques of four flavonoid carbon glycosides (orientin, isoorientin, vitexin, and isovitexin) from BLF were still confronted with difficulties due to their complex and similar structures, which obstructed the development of bamboo utilization. In this article, a purification technology of four flavonoid carbon glycosides from BLF by Sephadex LH-20 was improved. The results were evaluated by HPLC and pharmacological activity. Specifically, the eluent, flow rate, and loading amount were investigated, respectively. According to the results, the eluent would dominate the isolation effect among three factors. High concentration of isoorientin and four flavonoid carbon glycosides would be obtained under the optimized condition (The eluent was 70 % methanol, the loading amount was 1.5 g, and the flow rate was 0.5 mL/min). Meanwhile, the link between flavonoid carbon glycosides content and their antioxidant activity in vitro was also revealed. Overall, the results suggested that BLF may serve as potential functional food additives and medicine.